Transplants of cells and tissue engineered organs and tissues offer promise in facilitating tissue healing and repair and the replacement or treatment of diseased or dysfunctional organs. According to data from the American Association of Tissue Banks (AATB), a voluntary accreditation organization that sets standards for tissue banking, approximately 1.5 million bone and tissue allografts are distributed each year by AATB-accredited tissue banks in the United States. In the U.S., around 20,000 organ transplants are performed yearly, and the list of individuals in need of tissue and organ transplants is even increasing.
A primary challenge in the transplantation of tissues, organs, cells or an artificially created engineered tissue constructs is ensuring sufficient blood supply to the transplanted tissue and cells. In the absence of pre-existing vessels in the transplant capable of inosculation with the recipient blood supply, the amount of tissue that can be transplanted into a subject is limited by oxygen diffusion.
Ultimately, healthy transplants depend on sufficient vessel density within the transplanted tissue or organ and the organization of the vessels into a network comprised of low-resistance conduit vessels (arteries), a functional microcirculation (arterioles and capillaries) for a proper blood-tissue exchange, and drainage/compliance vessels (venules and veins).
Existing strategies for building a vascular system for tissue engineered constructs have been based on using cultured, human endothelial cells. For example, preparation of pre-formed vascular beds such as prevascularized constructs can be attached or incorporated at the tissue, organ or cell transplant interface at the time of transplantation as previously described in U.S. Pat. No. 7,052,829. However, growing such constructs is labor intensive and requires time for the prevascularized constructs to grow, which is not a possibility when it is necessary to transplant donated tissues, organs and cells within hours of removal of the organ, tissue or cell from a donor, or where the recipient is in need of an immediate cell or organ transplantation.
Additionally organs such as heart, kidneys, liver, lungs, pancreas, and intestines, and heart and lung transplants can be transplanted as whole organs. Many classifications of tissue may also be transplanted including whole eyes or corneas, heart valves, cardiovascular tissue, which includes the thoracic aorta, the abdominal aorta with iliac arteries, saphenous veins, and femoral vessels, may be donated to restore compromised blood circulation. Bone and soft musculoskeletal tissue, such as ligaments, are also suitable for transplantation for orthopedic and spinal surgeries and sports medicine injuries. Skin can be transplanted to promote healing and prevent infection in critically burned individuals, as well as whole, or partial face transplants for recipients who have severe facial deformities due to a previous injury. It is imperative that such large tissue and organ transplants are have sufficient blood supply to prevent atrophy of the transplanted tissue and integration into the recipients existing tissue.
Accordingly, improved methods for increasing vascularization of transplants such as donated and engineered tissues, cells and organs are needed.